ArticleThe Journal of clinical investigation2019
Integrin α5β1 regulates PP2A complex assembly through PDE4D in atherosclerosis.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Mechanosensors Collaborate to Regulate DNA Damage Repair in Hepatocellular Carcinoma.Cancer research · 2026Article
- Mechanobiology of the Hippo-YAP Signaling Network.Cold Spring Harbor perspectives in biology · 2026Article
- Multi-omics characterization of anoikis-related hub genes and macrophage-centered immune persistence with validation of HAVCR2 in atherosclerosis.Frontiers in immunology · 2026Article
- Tigloylgomisin P Inhibits Endothelial Inflammation by Regulating the NF-κB and Smad1/5/9 Pathways.Journal of lipid and atherosclerosis · 2026Article
- Elastin Regulation of Vasoreactivity in Resistance Arteries.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Integrin-Specific Signaling Drives ER Stress-Dependent Atherogenic Endothelial Activation.bioRxiv : the preprint server for biology · 2025Article
- The perspective of modern transplant science - transplant arteriosclerosis: inspiration derived from mitochondria associated endoplasmic reticulum membrane dysfunction in arterial diseases.International journal of surgery (London, England) · 2025Review
- Integrins as Drug Targets in Vascular and Related Diseases.International journal of drug discovery and pharmacology · 2024Article
- Integrin αProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Pathogenic mechanisms and therapeutic implications of extracellular matrix remodelling in cerebral vasospasm.Fluids and barriers of the CNS · 2023Review
- Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- Review
- The regulation and functions of the matricellular CCN proteins induced by shear stress.Journal of cell communication and signaling · 2023Review
- FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Vascular mechanotransduction.Physiological reviews · 2023Review
- [Research progress of matrix stiffness in regulating endothelial cell sprouting].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2023Review
- VPA mediates bidirectional regulation of cell cycle progression through the PPP2R2A-Chk1 signaling axis in response to HU.Cell death & disease · 2023Article
- Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease.Circulation research · 2023Review
- Actomyosin-mediated cellular tension promotes Yap nuclear translocation and myocardial proliferation through α5 integrin signaling.Development (Cambridge, England) · 2023Article
- Different roles of endothelial cell-derived fibronectin and plasma fibronectin in endothelial dysfunction.Turkish journal of medical sciences · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Fibronectin in the vascular wall promotes inflammatory activation of the endothelium during vascular remodeling and atherosclerosis. These effects are mediated in part by fibronectin binding to integrin α5, which recruits and activates phosphodiesterase 4D5 (PDE4D5) by inducing its dephosphorylation on an inhibitory site Ser651. Active PDE then hydrolyzes anti-inflammatory cAMP to facilitate inflammatory signaling. To test this model in vivo, we mutated the integrin binding site in PDE4D5 in mice. This mutation reduced endothelial inflammatory activation in athero-prone regions of arteries, and, in a hyperlipidemia model, reduced atherosclerotic plaque size while increasing markers of plaque stability. We then investigated the mechanism of PDE4D5 activation. Proteomics identified the PP2A regulatory subunit B55α as the factor recruiting PP2A to PDE4D5. The B55α-PP2A complex localized to adhesions and directly dephosphorylated PDE4D5. This interaction also unexpectedly stabilized the PP2A-B55α complex. The integrin-regulated, pro-atherosclerotic transcription factor Yap is also dephosphorylated and activated through this pathway. PDE4D5 therefore mediates matrix-specific regulation of EC phenotype via an unconventional adapter role, assembling and anchoring a multifunctional PP2A complex with other targets. These results are likely to have widespread consequences for control of cell function by integrins.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.